Control of cytoskeletal architecture by the src-suppressed C kinase substrate, SSeCKS

Cell Motil Cytoskeleton. 1998;41(1):1-17. doi: 10.1002/(SICI)1097-0169(1998)41:1<1::AID-CM1>3.0.CO;2-J.


Activation of protein kinase C (PKC) in many cell types results in cytoskeletal reorganization associated with cell proliferation. We previously described a new cell cycle-regulated myristylated PKC substrate, SSeCKS (pronounced essex), that interacts with the actin cytoskeleton [Lin et al., 1995, 1996]. SSeCKS shares significant homology with Gravin, which encodes kinase scaffolding functions for PKC and PKA [Nauert et al., 1997]. This article describes the cellular effects of ectopically expressing SSeCKS in untransformed NIH3T3 fibroblasts. Because the constitutive overexpression of SSeCKS is toxic [Lin et al., 1995], we developed cell lines with tetracycline (tet)-regulated SSeCKS expression. The induction of SSeCKS (removal of tet) caused significant cell flattening and the elaboration of an SSeCKS-associated cortical cytoskeletal matrix resistant to Triton X-100 extraction. Flattened cells were growth-arrested and marked by the formation of cellular projections and the temporary loss of actin stress fibers and vinculin-associated adhesion plaques. SSeCKS overexpression did not affect steady-state levels of actin, vinculin, or focal adhesion kinase (FAK) but did increase integrin-independent FAK tyrosine phosphorylation. Stress fiber loss was coincident with induced SSeCKS expression, strongly suggesting a direct effect. Cytochalasin, and to a lesser extent nocodazole, inhibited SSeCKS-induced cell flattening, however, only cytochalasin affected the shape of pre-flattened cells, suggesting a greater dependence on microfilaments, rather than microtubules. By contrast, only nocodazole caused retraction of the filopodia-like processes. These data indicate a role for SSeCKS in modulating both cytoskeletal and signaling pathways. Thus, we propose to expand SSeCKS scaffolding functions to include the ability to control actin-based cytoskeletal architecture, as well as mitogenic signal pathways.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • A Kinase Anchor Proteins
  • Actin Cytoskeleton* / drug effects
  • Actin Cytoskeleton* / physiology
  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases / analysis
  • Cell Adhesion
  • Cell Adhesion Molecules / metabolism
  • Cell Cycle Proteins*
  • Cell Division
  • Cell Size
  • Cytochalasin D / pharmacology
  • Enzyme Activation
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Gene Expression Regulation / drug effects
  • Mice
  • Microfilament Proteins / analysis
  • Microtubules / drug effects
  • Mitogen-Activated Protein Kinase 1
  • Mitogens / genetics
  • Mitogens / metabolism
  • Mitogens / physiology*
  • Nocodazole / pharmacology
  • Octoxynol
  • Protein Kinase C
  • Protein-Tyrosine Kinases / metabolism
  • Pseudopodia
  • Tensins
  • Tetracycline / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology


  • A Kinase Anchor Proteins
  • Akap12 protein, mouse
  • Cell Adhesion Molecules
  • Cell Cycle Proteins
  • Microfilament Proteins
  • Mitogens
  • Tensins
  • Cytochalasin D
  • Octoxynol
  • Protein-Tyrosine Kinases
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Ptk2 protein, mouse
  • Protein Kinase C
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Tetracycline
  • Tetradecanoylphorbol Acetate
  • Nocodazole